TY - JOUR
T1 - Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress
AU - Varzideh, Fahimeh
AU - Jankauskas, Stanislovas S.
AU - Kansakar, Urna
AU - Mone, Pasquale
AU - Gambardella, Jessica
AU - Santulli, Gaetano
N1 - Funding Information:
The Santulli lab is supported in part by the NIH (R01-HL159062, R01-DK123259, R01-HL146691, R01-DK033823, R56-AG066431, T32-HL144456, and R00-DK107895 to GS), the Irma T. Hirschl and Monique Weill-Caulier Trusts (to GS), and the Diabetes Action Research and Education Foundation (to GS). FV, SSJ and JG hold postdoctoral fellowships from the American Heart Association (AHA- 22POST915561, AHA-21POST836407, and AHA-20POST35211151, respectively). The authors apologize to all researchers whose relevant contributions were not cited owing to space limitations.
Funding Information:
The Santulli lab is supported in part by the NIH (R01-HL159062, R01-DK123259, R01-HL146691, R01-DK033823, R56-AG066431, T32-HL144456, and R00-DK107895 to GS), the Irma T. Hirschl and Monique Weill-Caulier Trusts (to GS), and the Diabetes Action Research and Education Foundation (to GS). FV, SSJ and JG hold postdoctoral fellowships from the American Heart Association (AHA 22POST915561, AHA-21POST836407, and AHA-20POST35211151, respectively). The authors apologize to all researchers whose relevant contributions were not cited owing to space limitations.
Publisher Copyright:
© 2022, Varzideh et al.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Sortilin is a glycoprotein mainly known for its role as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Its actual contribution to essential hypertension has remained hitherto elusive. Combining top-notch in vivo, ex vivo, and in vitro approaches to clinical investigations, Di Pietro et al. explored the signaling pathway evoked by sortilin in endothelial cells and report on such exploration in this issue of the JCI. The researchers identified circulating sortilin as a biomarker associated with high blood pressure. Mechanistically, they demonstrate that sortilin altered sphingolipid/ceramide homeostasis, initiating a signaling cascade that, from sphingosine-1-phosphate (S1P), leads to the augmented production of reactive oxygen species. Herein, we discuss the main implications of these findings, and we anticipate some of the potential avenues of investigation prompted by this discovery, which could eventually lead to treatments for cardiometabolic disorders.
AB - Sortilin is a glycoprotein mainly known for its role as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Its actual contribution to essential hypertension has remained hitherto elusive. Combining top-notch in vivo, ex vivo, and in vitro approaches to clinical investigations, Di Pietro et al. explored the signaling pathway evoked by sortilin in endothelial cells and report on such exploration in this issue of the JCI. The researchers identified circulating sortilin as a biomarker associated with high blood pressure. Mechanistically, they demonstrate that sortilin altered sphingolipid/ceramide homeostasis, initiating a signaling cascade that, from sphingosine-1-phosphate (S1P), leads to the augmented production of reactive oxygen species. Herein, we discuss the main implications of these findings, and we anticipate some of the potential avenues of investigation prompted by this discovery, which could eventually lead to treatments for cardiometabolic disorders.
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U2 - 10.1172/JCI156624
DO - 10.1172/JCI156624
M3 - Review article
C2 - 35104807
AN - SCOPUS:85124059480
VL - 132
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 3
M1 - e156624
ER -